Neural crest in development and repair
Author: Aquino, Jorge Benjamín
Date: 2007-11-09
Location: Samuelssonsalen, Tomtebodavägen 6, Solna Campus, Karolinska Institutet
Time: 09.30
Department: Institutionen för medicinsk biokemi och biofysik (MBB) / Department of Medical Biochemistry and Biophysics
View/ Open:
thesis.pdf (1.001Mb)
Abstract
This thesis is focused on several aspects of neural crest biology,
largely related to two main issues: 1) understanding its mechanisms of
migration and 2) analyzing the potential of neural crest stem cells or
their derivatives for nervous system repair. If repair is the aim,
knowledge of both timing and events leading to axonal degeneration is
required in order to block it and/or increase regeneration outcome. In
these studies I have made use of mouse, rat and chicken in vivo and in
vitro models to address specific questions regarding the scope of this
thesis.
In paper I, changes in distribution of myelin proteins are described
after ligation of the sciatic nerve, an injury model which does not allow
nerve regeneration to occur. Clustering of MBPs and P0 (the two most
abundant peripheral myelin proteins) was shown to precede their
degradation, involving subsequent roles of Schwann cells (SCs) and
macrophages in the removal of debris distally to the injury zone. Both
clustering and protein degradation steps were found to be accelerated in
young rat animals when compared to adult ones.
In paper II, similar kind of studies were applied in other two injury
models allowing regeneration to occur: a transient compression (crush) of
the nerve or an intraneural injection of colchicine, which transiently
blocks axonal transport. Changes in distribution of myelin (MBPs) and
axonal (PGP9.5) protein immunoreactivities were monitored for up to one
month and degeneration/regeneration processes followed and compared in
the two models. By applying the trophic factor apotransferrin we were
able to block the degeneration produced by colchicine, likely through
stabilization of axonal and/or SC cytoskeleton.
In paper III, original culture protocols have been applied to efficiently
generate highly pure cultures of mature SCs from boundary cap neural
crest stem cells (bNCSCs). The in vitro SC differentiation from stem
cells was found to resemble the in vivo process when looking at
combinations of markers changing expression during SC lineage. Stem
cell-derived SCs were able to myelinate axons both in vitro and in vivo.
These results prompted further work shown in paper V, in which the
regenerative potential of neural crest stem cell-derived SCs has been
tested in the contused spinal cord injury model. Even though in most
cases grafted cells died soon after transplantation, when grafted alive
they were found to improve locomotor behavior and to enhance endogenous
regenerative mechanisms, producing both an increase in axonal re-growth
and in recruitment of endogenous glial cells. In this study, evidences
are shown suggesting that after injury ependymal cells of the spinal cord
central canal can generate endogenous glial cells of myelinating
phenotype, likely including some of the Schwann like cells which populate
the injury zone allowing axonal re-growth.
In paper IV, the scaffolding protein Nedd9 is shown to be expressed by
multipotent migrating and post-migratory neural crest cells (NCCs). Nedd9
expression is induced in NCCs at the level of the dermamyotome dorsal
lip. Loss-of-function and gain-offunction studies were consistent with a
principal role for Nedd9 in NCC migration. Retinoic acid, known to be
synthesized by the dermamyotome, was found to induce Nedd9 expression in
NCCs. Nedd9 expression pattern in mouse is described in paper VI,
including mesencephalic ventral midbrain as well as other discrete
progenitor populations from diverse tissues and organs.
List of papers:
I. Setton-Avruj CP, Aquino JB, Goedelman CJ, Soto EF, Villar MJ (2002). "P0 and myelin basic protein-like immunoreactivities following ligation of the sciatic nerve in the rat." Neurochem Res 27(11): 1293-303
Pubmed
II. Aquino JB, Musolino PL, Coronel MF, Villar MJ, Setton-Avruj CP (2006). "Nerve degeneration is prevented by a single intraneural apotransferrin injection into colchicine-injured sciatic nerves in the rat." Brain Res 1117(1): 80-91. Epub 2006 Sep 28
Pubmed
III. Aquino JB, Hjerling-Leffler J, Koltzenburg M, Edlund T, Villar MJ, Ernfors P (2006). "In vitro and in vivo differentiation of boundary cap neural crest stem cells into mature Schwann cells." Exp Neurol 198(2): 438-49. Epub 2006 Jan 25
Pubmed
IV. Aquino J.B, Lallemend F, Marmigère F, Adameyko I, Golemis E.A, Ernfors P (2007). "Dynamic levels of the signaling molecule Nedd9 functions with integrins to specify cell migration in neural crest cells." (Manuscript)
V. Erschbamer M, Aquino JB, Hjerling-Leffler J, Ernfors P, Olson L (2007). "Mouse stem cell-derived Schwann cells promote recovery after spinal cord contusion injury in rats." (Manuscript)
VI. Aquino JB, Marmigère F, Villar M.J, Wagner M, Ernfors P (2007). "Differential expression and dynamic changes in murine Nedd9 identifies progenitors of diverse tissues." (Manuscript)
I. Setton-Avruj CP, Aquino JB, Goedelman CJ, Soto EF, Villar MJ (2002). "P0 and myelin basic protein-like immunoreactivities following ligation of the sciatic nerve in the rat." Neurochem Res 27(11): 1293-303
Pubmed
II. Aquino JB, Musolino PL, Coronel MF, Villar MJ, Setton-Avruj CP (2006). "Nerve degeneration is prevented by a single intraneural apotransferrin injection into colchicine-injured sciatic nerves in the rat." Brain Res 1117(1): 80-91. Epub 2006 Sep 28
Pubmed
III. Aquino JB, Hjerling-Leffler J, Koltzenburg M, Edlund T, Villar MJ, Ernfors P (2006). "In vitro and in vivo differentiation of boundary cap neural crest stem cells into mature Schwann cells." Exp Neurol 198(2): 438-49. Epub 2006 Jan 25
Pubmed
IV. Aquino J.B, Lallemend F, Marmigère F, Adameyko I, Golemis E.A, Ernfors P (2007). "Dynamic levels of the signaling molecule Nedd9 functions with integrins to specify cell migration in neural crest cells." (Manuscript)
V. Erschbamer M, Aquino JB, Hjerling-Leffler J, Ernfors P, Olson L (2007). "Mouse stem cell-derived Schwann cells promote recovery after spinal cord contusion injury in rats." (Manuscript)
VI. Aquino JB, Marmigère F, Villar M.J, Wagner M, Ernfors P (2007). "Differential expression and dynamic changes in murine Nedd9 identifies progenitors of diverse tissues." (Manuscript)
Issue date: 2007-10-19
Rights:
Publication year: 2007
ISBN: 978-91-7357-367-2
Statistics
Total Visits
Views | |
---|---|
Neural ...(legacy) | 656 |
Neural ... | 142 |
Total Visits Per Month
October 2023 | November 2023 | December 2023 | January 2024 | February 2024 | March 2024 | April 2024 | |
---|---|---|---|---|---|---|---|
Neural ... | 3 | 2 | 0 | 0 | 0 | 5 | 2 |
File Visits
Views | |
---|---|
thesis.pdf(legacy) | 556 |
thesis.pdf | 231 |
thesis.pdf.txt(legacy) | 2 |
Top country views
Views | |
---|---|
United States | 296 |
Germany | 65 |
Sweden | 60 |
Argentina | 42 |
China | 42 |
Finland | 20 |
South Korea | 19 |
United Kingdom | 15 |
Denmark | 9 |
Ireland | 9 |
Top cities views
Views | |
---|---|
Sunnyvale | 31 |
Romeo | 27 |
Kiez | 20 |
Beijing | 19 |
Seoul | 19 |
Buenos Aires | 16 |
Dublin | 9 |
Helsinki | 9 |
Mountain View | 9 |
Stockholm | 8 |